The structures themselves may one day lead to new therapies, since the proteins are important regulators of genes essential for development and reproduction and are implicated in cancer and other diseases. Furthermore, the work provides biologists with a first glimpse of a synergistic folding mechanismwhich may be a commonplace occurrence in the cell.
The two proteins are a nuclear receptor coactivator and the general transcription coactivator called CBP, and their structure is reported in the current issue of the journal Nature by a group led by Peter E. Wright, Ph.D., who is Professor and Chairman of the Department of Molecular Biology and Cecil H. and Ida M. Green Investigator in Medical Research at TSRI.
"This [synergistic folding] is something that has never been seen before," says Wright. "We have always thought about proteins in terms of their shape, their 3-D fold. It was always assumed that the structures of proteins are responsible for their biological functions."
"We can no longer just equate structure with function," he says.
If cells are the tiny factories of life, proteins are the workers, machines, bricks, and mortar of those factories. For years biologists have solved the structures of proteins as a way of elucidating their mechanisms and understanding life on the molecular scale.
But it is now recognized that many of the proteins in the human genome are normally unstructured in the cell. By some estimates, 30 to 40 percent of the human genome codes for proteins that have either large unstructured regions or are entirely unstructured and yet are biologically functional, and there is growing evidence that much of biology is carried out by these "intrinsical
Contact: Robin B. Goldsmith
Scripps Research Institute